Registry Study of Revcovi Treatment in Patients With ADA-SCID

Single Arm, Open-Label, Multicenter, Registry Study of Revcovi (Elapegademase-lvlr) Treatment in ADA-SCID Patients Requiring Enzyme Replacement Therapy

This registry is conducted in patients with adenosine deaminase severe combined immune deficiency (ADA-SCID) treated with Revcovi™ to collect periodic clinical and biochemical data on safety and dose adjustment.

Study Overview

• Status: Completed
• Conditions: Severe Combined Immunodeficiency; Adenosine Deaminase Deficiency
• Intervention / Treatment: Biological: elapegademase-lvlr

Detailed Description

Patients with ADA-SCID who require treatment with Revcovi as Enzyme Replacement Therapy (ERT) will be followed until the last enrolled patient has reached a minimum of 24 months of Revcovi treatment or until undergoing HSCT or HSCGT, whichever occurs first.

Patients undergoing HSCT or HSC-GT will be followed one month after last Revcovi dose and again at six months to assess adverse events (AEs) and survival. Throughout the duration of the study, patients will be assessed continually for AEs.

Patients/Parents/Caregivers will self-administer weekly intramuscular (IM) dose(s) of Revcovi and will be followed according to the Suggested Schedule of Assessments for trough dAXP and ADA activity. Treatment dosing and monitoring will be individualized per provider and patient characteristics in adherence with each study sites' standards of care.

Patients in the Phase 3 Revcovi™ study (STP-2279-002) will be given the opportunity to enroll in this registry study and proceed to the Treatment Month 6 Visit per the Suggested Schedule of Assessments for Adagen-Transitioning Patients.

• Study Type: Observational
• Enrollment (Actual): 32

Contacts and Locations

• Study Contact: Name: Chiesi Clinical Trial Info; Phone Number: +39.0521 2791; Email: clinicaltrials_info@chiesi.com
• Study Contact Backup: Name: Caroline Fradette; Phone Number: 1-514-451-1217; Email: c.fradette@chiesi.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1752
      • University of California Los Angeles
    • San Diego, California, United States, 92123
      • Allergy & Asthma Medical Group and Research Center, A P.C.
    • San Francisco, California, United States, 94158
      • UCSF - University of California
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • University of South Florida Allergy Immunology Clinic
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Childrens Hospital of New Orleans
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital - Washington University School of Medicine
  • New York
    • Buffalo, New York, United States, 14203
      • UBMD Pediatrics Outpatient Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Children's Hospital
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Le Bonheur Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98101
      • Seattle Children's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

There are four types of patients with ADA-SCID who may be eligible for treatment with Revcovi, including:

• Patients currently receiving chronic ERT with Adagen
• Infants diagnosed via newborn screening and/or definitive testing for ADA deficiency
• Patients preparing for HSCT or HSC-GT
• Patients who decline, are ineligible or do not respond to HSCT or HSC-GT

Description

Inclusion Criteria:

• Patients currently receiving chronic ERT with Adagen® and transitioned/transitioning to Revcovi;
• Infants diagnosed via newborn screening and definitive testing for ADA deficiency prescribed Revcovi;
• Patients receiving Revcovi while preparing for Hematopoietic Stem Cell Transplant (HSCT) or Hematopoietic Stem Cell Gene Therapy (HSCGT)
• Patients who decline, are ineligible or do not respond to HSCT or HSC-GT and resume/start Revcovi.

Exclusion Criteria:

• Any condition that, in the opinion of the Investigator, makes the patient unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

ERT with ADA; Patients with diagnosis of ADA-SCID treated with ERT with Revcovi or transitioning to Revcovi from Adagen

Biological: elapegademase-lvlr; Patients transitioning from Adagen: For patients currently receiving Adagen at ≤ 30 U/kg/wk or an unknown Adagen dose, the suggested dosage of Revcovi is 0.2 mg/kg/wk IM. For patients currently receiving Adagen at > 30 U/kg/wk the suggested equivalent Revcovi dosage (mg/kg/wk) is the Adagen dosage in U/kg/wk divided by 150. At the investigator's discretion, the total weekly dose may be divided and administered in multiple IM injections, increased by 0.033 mg/kg/wk if trough ADA activity is < 30 mmol/hr/L, dAXP is > 0.02 mmol/L, and/or the immune reconstitution is inadequate. Adagen-naïve patients: The suggested starting Revcovi dosage is 0.2 mg/kg twice weekly IM based on ideal body weight, for a minimum of 12 to 24 weeks until immune reconstitution is achieved. At the investigator's discretion, the dosage may be gradually increased to maintain trough ADA activity > 30 mmol/hr/L, dAXP < 0.02 mmol/L, and/or to maintain adequate immune reconstitution.; Other Names: Revcovi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deoxyadenosine nucleotides (dAXP) activity	Total trough erythrocyte dAXP activity	Month 24
ADA activity	Trough plasma ADA activity	Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune status (SSA/PI)	Absolute lymphocyte count and subset B, T, and NK analysis. Immunoglobulin (Ig) concentrations (IgG, IgA, and IgM). Measurement of immune response at Investigator discretion.	Month 24
Clinical status	Infections (clinically or microbiologically documented) Incidence and duration of hospitalizations Growth for patients < 18 years old Overall survival through the end of study	Month 24
Safety assessed by determining adverse events (AEs), serious adverse events (SAEs)	Assessed by determining adverse events (AEs), serious adverse events (SAEs), clinical signs and symptoms from physical examinations, and laboratory examinations	Month 24

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2019
• Primary Completion (Actual): January 18, 2023
• Study Completion (Actual): January 18, 2023

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 13, 2019
• First Posted (Actual): March 18, 2019

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Primary Immunodeficiency Diseases; Severe Combined Immunodeficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Adenosine Deaminase Inhibitors; Elapegademase
• Other Study ID Numbers: CLI-06814AA1-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No